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A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling
Gao, Jian1,2; Zhang, Kunlin3,4; Wang, Yi5; Guo, Rui5; Liu, Hao5; Jia, Caixia1; Sun, Xiaoli1; Wu, Chaoyong1; Wang, Wei1; Du, Jie6,7; Chen, Jianxin1
First AuthorJian Gao
Correspondent Emailcjx@bucm.edu.cn (j. chen)
2020-05-01
Source PublicationPHARMACOLOGICAL RESEARCH
ISSN1043-6618
SubtypeArticle
Volume155Pages:13
QuartileQ1
Contribution Rank3
Abstract

Cardiac hypertrophy (CH) is an enormous risk factor in the process of heart failure development, however, there is still lack of effective treatment for CH. Mitochondrial protection is an effective way against CH. Rheum palmatum L. (rhubarb) has been used to treat chronic heart diseases such as heart failure, especially to inhibit cardiac compensatory enlargement. The aim of this study was to explore the pharmacodynamic component of rhubarb and reveal its pharmacological effects and targets in the treatment of CH. Based on network pharmacology and machine learning approach, ingredients of rhubarb and targets for CH were extracted and surflex docking was conducted for obtaining the optimal ingredient-target combination(s) and emodin-SIRT3 was identified for further functional analysis. Transverse aortic constriction or isoproterenol induced CH mice and phenylephrine injured cardiomyocytes were used to verify the mitochondria protection effect and CH improvement of emodin in vivo and in vitro by modulation of mitochondrial SIRT3 signaling. The results showed that emodin could block agonist-induced and pressure overload-mediated CH. Emodin prevented mitochondrial dysfunction and its underlying mechanism was attributed to the activation of SIRT3, but the effect was not obvious with the presence of SIRT3 inhibitors (3-TYP)/SIRT3 siRNA. Furthermore, PGC-1a was involved in the process of emodin regulating SIRT3 signaling pathway as an upstream target. Our findings clarified the main material basis and mechanism of rhubarb in the treatment of CH. Emodin, as the major ingredient of rhubarb, has therapeutic potential for CH through mitochondrial protection due to the modulation of SIRT3 signaling.

KeywordRheum palmatum L. Emodin Cardiac hypertrophy SIRT3 Mitochondrial dysfunction
DOI10.1016/j.phrs.2020.104739
Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China
Funding ProjectNational Natural Science Foundation of China[81522051] ; National Natural Science Foundation of China[81774151] ; National Natural Science Foundation of China[81822047]
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000527701100004
PublisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS KeywordOXIDATIVE STRESS ; ACTIVATION ; FOXO3A ; INFLAMMATION ; DEACETYLASE ; MECHANISMS ; APOPTOSIS ; PROTECTS ; CELLS ; HEART
Citation statistics
Cited Times:5[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/31702
Collection中国科学院心理健康重点实验室
Corresponding AuthorChen, Jianxin
Affiliation1.Beijing Univ Chinese Med, 11 Bei San Huan Dong Lu, Beijing 100029, Peoples R China
2.Beijing Univ Chinese Med, Affiliated Hosp 3, Beijing 100029, Peoples R China
3.Chinese Acad Sci, Ctr Genet & BioMed Informat Res, Inst Psychol, CAS Key Lab Mental Hlth, Beijing 100101, Peoples R China
4.Univ Chinese Acad Sci, Dept Psychol, Beijing 100049, Peoples R China
5.Zhejiang Univ, 866 Yuhangtang Rd, Hangzhou 310058, Peoples R China
6.Minist Educ, Key Lab Remodeling Related Cardiovasc Dis, Beijing 100029, Peoples R China
7.Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing 100029, Peoples R China
Recommended Citation
GB/T 7714
Gao, Jian,Zhang, Kunlin,Wang, Yi,et al. A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling[J]. PHARMACOLOGICAL RESEARCH,2020,155:13.
APA Gao, Jian.,Zhang, Kunlin.,Wang, Yi.,Guo, Rui.,Liu, Hao.,...&Chen, Jianxin.(2020).A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling.PHARMACOLOGICAL RESEARCH,155,13.
MLA Gao, Jian,et al."A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling".PHARMACOLOGICAL RESEARCH 155(2020):13.
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